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The original inhabitants of Pandora, the Eridians imprisoned The Destoyer in the Vault to keep it from destroying the universe. The Guardian Angel sent out a signal to bring the Vault Hunters to Pandora in an attempt to lure them into collecting the pieces of the Vault Key and killing The Destroyer.
At the end of Borderlands the player confronts Commandant Steele at the entrance to The Vault. She uses the Vault Key to open the portal to the Vault, however The Destroyer bursts through the portal and kills Steele. The Guardian Angel tells the player that within the dimension of the Vault The Destroyer would be invincible, however outside it was completely vulnerable. The player defeats The Destroyer, and is thanked by the Guardian Angel.
The Destroyer is very similar to the Gene Worm, a creature from Half-Life: Opposing Force, the first game that Gearbox Software, creators of Borderlands, worked on. They are both the final bosses of their games, both creatures have an amorphous body and tentacles, both creatures have a similar orb-like weak point, and both are mysterious aliens.